Our objective was to increase muscle mass in pigs. To achieve this goal we produced transgenic pigs carrying a fusion gene consisting of the regulatory sequences derived from the avian skeletal α-actin (SK733) gene and cDNA encoding a human insulin-like growth factor-I (IGF-I). The gene was specifically designed to target striated muscle. This fusion gene was previously transferred into mice to induce muscle fiber hypertrophy. The SK733/IGF-I transgene was microinjected into 1207 pig zygotes and the zygotes were transferred into 51 recipients. A total of 167 pigs were farrowed by 27 recipients. Of 17 transgenic pigs identified by Southern blot analysis, 12 are living and are being mated to non-transgenic pigs to produce G1 progeny. To assess transgene expression, muscle biopsies of the longissimus dorsi were taken when pigs reached 80-100 kg body weight. Muscle samples were frozen in liquid nitrogen, powdered, and then aliquoted for isolation of total RNA and determination of IGF-I content using immunoradiometric assay. All but one of the 12 transgenic pigs expressed the IGF-I transgene. Northern blot analysis of total RNA revealed an abundant mRNA species of approximately 1.1 kb from transgenic pigs that was not present in RNA samples from littermate control pigs. Muscle IGF-I concentrations varied from 20 to 1702 ng/g muscle in transgenic pigs compared to less than 10 ng/g muscle in non-transgenic control pigs. Muscle IGF-I concentrations were in general agreement with abundance of IGF-I mRNA of Northern blots. Serum IGF-I concentrations in transgenic pigs (160 ± 6.8 ng/ml) did not differ from that of littermate control pigs (143 ± 6.5 ng/ml). Daily weight gain from 20 to 60 kg body weight was similar for transgenic and littermate control pigs (865 ± 29.6 g versus 876 ± 18.9 g/day). Definitive differences in phenotype of transgenic and control pigs were not detected, and no gross abnormalities, pathologies, or health-related problems have been encountered to date. In summary, these data indicate that expression vectors based on the avian skeletal α-actin gene can drive expression of regulatory proteins in skeletal muscle. This has implications for the study of muscle physiology and for investigation of factors that may impact meat animal production.